Diseases of the central nervous system (CNS) are widespread. The National Institute of Mental Health recently estimated that neurological disorders affect 22% of the adult population in the United States and account for 30% of the total health care budget each year.
Traumatic Brain Injury (TBI), and Stroke are such CNS diseases and are characterized by the need for immediate short term drug therapy. Traumatic Brain Injury (TBI) is caused primarily by a traumatic blow to the head causing damage to the brain, often without penetrating the skull. The initial trauma can result in expanding hematoma, subarachnoid hemorrhage, cerebral edema, raised intracranial pressure (ICP), and cerebral hypoxia, which can, in turn, lead to severe secondary events due to low cerebral blood flow (CBF). Half of the people with TBI die before reaching the hospital and from those that survive, a large percentage suffer serious neurologic disorders.
Stroke is the destruction of brain tissue due to impaired blood supply caused by intracerebral hemorrhage, thrombosis (clotting), or embolism (obstruction caused by clotted blood or other foreign matter circulating in the bloodstream). Stroke is a common cause of death in the United States. The deleterious effects of a stroke are comparable to those caused by TBI.
The use of drugs in neurological illness has been studied extensively over the last century. As a result, many therapeutic agents exist today for the treatment of central nervous system (CNS) diseases including Traumatic Brain Injury (TBI), and Stroke. These include: (a) nonsteroidal anti-inflammatory agents (aspirin, acetaminophen, indomethacin, ibuprofen), (b) steroid anti-inflammatory agents (cortisone, prednisone, prednisolone, dexamethasone), (c) antioxidants (superoxide dismutase, catalase, nitric oxide, mannitol), (d) calcium channel blockers (nimodipine, nifedipine, verapamil, nicardipine, isradipine), and (e) neurotrophic factors (endorphins, citicholine).
However, delivering a drug to a therapeutic site of action within the central nervous system (CNS) can be very difficult because of the numerous chemical and physical barriers which must be overcome in order for such a delivery to be successful. The blood brain barrier (BBB) presents the primary obstacle in delivering drugs to the brain. Other limiting parameters involve the short half-life of drugs and the lack of appropriate drug concentrations reaching a localized area in the brain. Currently, attempts are being made to deliver drugs to the brain via either disruption of the BBB through chemical means, intracerebral delivery using infusion pumps, or direct delivery to the CNS through implantation of fetal neural tissue. Each of these methods have possible deficiencies as evidenced by toxic side-effects, dimensional complications, lack of reliability and high cost.
To date, methods for delivering drugs to the brain have not been completely effective.